Repeated administration of high doses of cocaine to rats, produces a persistent decrease in dopamine transport receptors in the frontal cortex. This may be relevant to cocaine reward, as dopamine transport receptor has been identified as the neuronal structure and the frontal cortex, as an anatomical site mediating the reinforcing effects of cocaine. In this study we have investigated the effect of cocaine on dopamine transport receptors in humans. Frontal cortex was obtained from post-mortem brains of 13 cocaine addicts with a positive and from 13 normals, with a negative blood screen for cocaine. P2 fractions prepared from pulverized frontal cortex, were assayed for the DATR binding with [3H]GBR 12935. The Scatchard analysis indicated a 34% decrease in Bmax with no change in KD. The decrease in DATR may reflect a reduction in DA terminals and supports the hypothesis that cocaine use results in DA depletion associated with the loss of DA terminals.